When PD progresses, increasing GOOD ON time can help alleviate the burden of motor complications

As the therapeutic window of levodopa narrows during PD progression, daily disruptions become more frequent and unpredictable1,2

Chart showing the narrowing therapeutic response window of levodopa through Parkinson's disease progression.
Graphic showing 50%

of patients with PD experience OFF, dyskinesia, or both within 5 years after starting levodopa3

Widening the therapeutic window by simultaneously treating both OFF time and dyskinesia can increase patients’ overall GOOD ON time1,2,4

Chart showing that widening the therapeutic response window of levodopa can increase patients' overall GOOD ON time.

Increasing GOOD ON time had a direct positive impact on patients’ daily lives

With more GOOD ON time, patients observed the following changes*,5-7

More independence in performing activities of daily living

Fewer uncontrolled
motor symptoms

Fewer disruptions while in a public or social setting

*There are no studies showing that GOCOVRI affects specific outcomes above.

When motor complications occur, it may be beneficial to consider adding an NMDA, N-methyl-D-aspartate, antagonist (glutamatergic pathway) to complement the current dopaminergic treatment regimen.*,8

*The mechanism by which amantadine exerts efficacy in the treatment of dyskinesia and OFF time in patients with PD is unknown.4

Understanding the role of glutamate in PD

Dopamine is only part of the story when it comes to controlling motor complications.8

  • NMDA Receptor
  • Glutamate
  • Dopamine Receptor
  • Dopamine
  • NMDA Antagonist

Reducing glutamate hyperactivity through the NMDA receptor could be critical to reducing dyskinesia and OFF time†,8

NMDA. A synthetic amino acid C5N9NO4 that binds selectively to a subset of glutamate receptors on neurons.17

†The mechanism by which amantadine exerts efficacy in the treatment of dyskinesia and OFF time in patients with PD is unknown.4

How amantadine is believed to work

AMANTADINE IS AN NMDA ANTAGONIST USED IN PD TREATMENT‡,18,19

  • Amantadine is used for symptomatic treatment for PD and can reduce levodopa-induced dyskinesia and OFF time18,21,22
  • The mechanism by which amantadine exerts efficacy in the treatment of dyskinesia and OFF time in patients with PD is unknown4
    • May work by reducing excessive glutamatergic activity, which contributes to dyskinesia and OFF time10
    • Amantadine may have direct and indirect effects on dopamine neurons; it exerts dopaminergic-like side effects such as hallucinations and dizziness in humans18
  • Common daily dosing of amantadine HCl IR in PD is 100 mg BID18
  • NMDA Receptor
  • Glutamate
  • Dopamine Receptor
  • Dopamine
  • NMDA Antagonist
Illustration of the effect of amantadine on glutamate hyperactivity through the NMDA receptor during dyskinesia.

‡Amantadine is a low-affinity, noncompetitive NMDA antagonist, which means inhibition of the NMDA channel occurs at a different binding site than the active site where the substrate binds.18-20

Get the conversation going about motor complications

Managing dyskinesia and OFF time begins with a discussion among you, your patient, and their care partner.

Your patients may not always be forthcoming about the difficulties they face with dyskinesia and OFF time. There are many reasons for this behavior. Keep in mind that your patients may:

  • Downplay their dyskinesia to avoid OFF time
  • Not realize the impact or effects of their dyskinesia or OFF time
  • Believe dyskinesia is just a sign of disease progression
  • Assume there are no dyskinesia treatment options

The following may indicate that your patients struggle with dyskinesia and OFF time:

  • They make comments that imply compromise or settling
  • Describing unpredictable episodes of dyskinesia, ON, and OFF time
  • Referring to ON time negatively
  • An increase in "accident prone" behaviors
  • Difficulties with activities or hobbies
  • Feeling embarrassed in social situations
  • Care partner makes comments about movement control
  • Difficulties at work

Download our discussion guide

Have your patients fill it out to give you a better understanding of how dyskinesia and OFF time are impacting their day.

Download

What efficacy data does GOCOVRI have?

GOCOVRI is backed by 2 Phase 3 clinical trials. These studies assessed the ability of GOCOVRI to reduce dyskinesia (primary endpoint), reduce OFF time (secondary endpoint), and increase GOOD ON time (secondary endpoint).4,22,23

See Efficacy Data

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Important Safety Information

IMPORTANT SAFETY INFORMATION AND INDICATION

CONTRAINDICATIONS

GOCOVRI is contraindicated in patients with creatinine clearance below 15 mL/min/1.73 m2.

WARNINGS AND PRECAUTIONS

Falling Asleep During Activities of Daily Living and Somnolence: Patients treated with Parkinson’s disease medications have reported falling asleep during activities of daily living. If a patient develops daytime sleepiness during activities that require full attention (e.g., driving a motor vehicle, conversations, eating), GOCOVRI should ordinarily be discontinued or the patient should be advised to avoid potentially dangerous activities.

Suicidality and Depression: Monitor patients for depression, including suicidal ideation or behavior. Prescribers should consider whether the benefits outweigh the risks of treatment with GOCOVRI in patients with a history of suicidality or depression.

Hallucinations/Psychotic Behavior: Patients with a major psychotic disorder should ordinarily not be treated with GOCOVRI because of the risk of exacerbating psychosis. Observe patients for the occurrence of hallucinations throughout treatment, especially at initiation and after dose increases.

Dizziness and Orthostatic Hypotension: Monitor patients for dizziness and orthostatic hypotension, especially after starting GOCOVRI or increasing the dose.

Withdrawal-Emergent Hyperpyrexia and Confusion: Rapid dose reduction or abrupt discontinuation of GOCOVRI, may cause an increase in the symptoms of Parkinson’s disease or cause delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, or slurred speech. Avoid sudden discontinuation of GOCOVRI.

Impulse Control/Compulsive Behaviors: Patients may experience urges (e.g. gambling, sexual, money spending, binge eating) and the inability to control them. It is important for prescribers to ask patients or their caregivers about the development of new or increased urges. Consider dose reduction or stopping medications.

ADVERSE REACTIONS

The most common adverse reactions (>10%) were hallucination, dizziness, dry mouth, peripheral edema, constipation, fall, and orthostatic hypotension.

INDICATION

GOCOVRI® (amantadine) extended release capsules is indicated:

  • For the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications
  • As adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes

It is not known if GOCOVRI is safe and effective in children.

Please see full Prescribing Information and Patient Information.

Abbreviations: BID, 2 times a day; IR, immediate release; OLE, open-label extension; PD, Parkinson's disease; QID, 4 times a day; TID, 3 times a day.

References: 1. Elkurd MT, Bahroo LB, Pahwa R. The role of extended-release amantadine for the treatment of dyskinesia in Parkinson's disease patients. Neurodegener Dis Manag. 2018;8(2):73-80. doi:10.2217/nmt-2018-0001 2. Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson disease: a review. JAMA. 2020;323(6):548-560. doi:10.1001/jama.2019.22360 3. Bjornestad A, Forsaa EB, Pedersen KF, Tysnes OB, Larsen JP, Alves G. Risk and course of motor complications in a population-based incident Parkinson's disease cohort. Parkinsonism Relat Disord. 2016;22:48-53. doi:10.1016/j.parkreldis.2015.11.007 4. GOCOVRI® (amantadine). Prescribing Information. Adamas Pharma LLC; 2021. 5. Jimenez Shahed J, Merola A, Malaty I, et al. The clinical and humanistic value of “good on-time” among patients with advanced Parkinson's disease: a real-world study from 7 countries. Poster presented at: American Academy of Neurology Annual Meeting; April 2-7, 2022; Seattle, WA. 6. Deal LS, Flood E, Myers DE, Devine J, Gray DL. The Parkinson's Disease Activities of Daily Living, Interference, and Dependence instrument. Mov Disord Clin Pract. 2019;6(8):678-686. doi:10.1002/mdc3.12833 7. Davis Phinney Foundation. The difference between dyskinesia and tremor. Accessed January 3, 2023. https://davisphinneyfoundation.org/the-difference-between-dyskinesia-andtremor/ 8. Encarnacion EV, Hauser RA. Levodopa-induced dyskinesias in Parkinson's disease: etiology, impact on quality of life, and treatments. Eur Neurol. 2008;60(2):57-66. doi:10.1159/000131893 9. Rajan R, Popa T, Quartarone A, Ghilardi MF, Kishore A. Cortical plasticity and levodopa-induced dyskinesias in Parkinson's disease: connecting the dots in a multicomponent network. Clin Neurophysiol. 2017;128(6):992-999. doi:10.1016/j.clinph.2017.03.043 10. Duty S. Targeting glutamate receptors to tackle the pathogenesis, clinical symptoms and levodopa-induced dyskinesia associated with Parkinson's disease. CNS Drugs. 2012;26(12):1017-1032. doi:10.1007/s40263-012-0016-z 11. Gerfen CR, Surmeier DJ. Modulation of striatal projection systems by dopamine. Annu Rev Neurosci. 2011;34:441-466. doi:10.1146/annurev-neuro-061010-113641 12. Surmeier DJ, Ding J, Day M, Wang Z, Shen W. D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci. 2007;30(5):228-235. doi:10.1016/j.tins.2007.03.008 13. Ahmed I, Bose SK, Pavese N, et al. Glutamate NMDA receptor dysregulation in Parkinson's disease with dyskinesias. Brain. 2011;134(4):979-986. doi:10.1093/brain/awr028 14. Sharma VD, Lyons KE, Pahwa R. Amantadine extended-release capsules for levodopa-induced dyskinesia in patients with Parkinson's disease. Ther Clin Risk Manag. 2018;14:665-673. doi:10.2147/TCRM.S144481 15. Manson A, Stirpe P, Schrag A. Levodopa-induced-dyskinesias clinical features, incidence, risk factors, management and impact on quality of life. J Parkinsons Dis. 2012;2(3):189-198. doi:10.3233/JPD-2012-120103 16. Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson's disease (2009). Neurology. 2009;72(21 Suppl 4):S1-S136. doi:10.1212/WNL.0b013e3181a1d44c 17. National Library of Medicine, PubChem. NIH. N-methyl-D-aspartic acid. https://pubchem.ncbi.nlm.nih.gov/compound/22880. Accessed October 9, 2023. 18. Symmetrel® (amantadine hydrochloride, USP). Prescribing Information. Endo Pharmaceuticals Inc. 19. Parsons CG, Quack G, Bresink I, et al. Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor impairment activity in vivo. Neuropharmacology. 1995;34(10):1239-1258. doi:10.1016/0028-3908(95)00092-k 20. Blanpied TA, Clarke RJ, Johnson JW. Amantadine inhibits NMDA receptors by accelerating channel closure during channel block. J Neurosci. 2005;25(13):3312-3322. doi:10.1523/JNEUROSCI.4262-04.2005 21. Crosby N, Deane KH, Clarke CE. Amantadine in Parkinson's disease. Cochrane Database Syst Rev. 2003;(1):CD003468. doi:10.1002/14651858.CD003468 22. Elmer LW, Juncos JL, Singer C, et al. Pooled analyses of phase III studies of ADS-5102 (amantadine) extended-release capsules for dyskinesia in Parkinson's disease. CNS Drugs. 2018;32(4):387-398. doi:10.1007/s40263-018-0498-4 23. Tanner CM, Pahwa R, Hauser RA, et al. EASE LID 2: a 2-year open-label trial of Gocovri (amantadine) extended release for dyskinesia in Parkinson's disease. J Parkinsons Dis. 2020;10(2):543-558. doi:10.3233/JPD-191841

Important Safety Information

IMPORTANT SAFETY INFORMATION AND INDICATION

CONTRAINDICATIONS

GOCOVRI is contraindicated in patients with creatinine clearance below 15 mL/min/1.73 m2.

WARNINGS AND PRECAUTIONS

Falling Asleep During Activities of Daily Living and Somnolence: Patients treated with Parkinson’s disease medications have reported falling asleep during activities of daily living. If a patient develops daytime sleepiness during activities that require full attention (e.g., driving a motor vehicle, conversations, eating), GOCOVRI should ordinarily be discontinued or the patient should be advised to avoid potentially dangerous activities.

Suicidality and Depression: Monitor patients for depression, including suicidal ideation or behavior. Prescribers should consider whether the benefits outweigh the risks of treatment with GOCOVRI in patients with a history of suicidality or depression.

Hallucinations/Psychotic Behavior: Patients with a major psychotic disorder should ordinarily not be treated with GOCOVRI because of the risk of exacerbating psychosis. Observe patients for the occurrence of hallucinations throughout treatment, especially at initiation and after dose increases.

Dizziness and Orthostatic Hypotension: Monitor patients for dizziness and orthostatic hypotension, especially after starting GOCOVRI or increasing the dose.

Withdrawal-Emergent Hyperpyrexia and Confusion: Rapid dose reduction or abrupt discontinuation of GOCOVRI, may cause an increase in the symptoms of Parkinson’s disease or cause delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, or slurred speech. Avoid sudden discontinuation of GOCOVRI.

Impulse Control/Compulsive Behaviors: Patients may experience urges (e.g. gambling, sexual, money spending, binge eating) and the inability to control them. It is important for prescribers to ask patients or their caregivers about the development of new or increased urges. Consider dose reduction or stopping medications.

ADVERSE REACTIONS

The most common adverse reactions (>10%) were hallucination, dizziness, dry mouth, peripheral edema, constipation, fall, and orthostatic hypotension.

INDICATION

GOCOVRI® (amantadine) extended release capsules is indicated:

  • For the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications
  • As adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes

It is not known if GOCOVRI is safe and effective in children.

Please see full Prescribing Information and Patient Information.